Current clinical management of multiple myeloma (MM) relies on bone marrow (BM) biopsies for minimal residual disease (MRD) assessment. While BM biopsies are the gold standard, their invasive nature and potential to miss extramedullary or patchy disease necessitate sensitive, non-invasive liquid biopsy platforms.

In this study, we evaluated the analytical performance of the CellSearch® CMMC assay to determine its utility for deep-MRD monitoring. Using a standard 4 mL whole blood input, the assay achieves a WBC-normalized sensitivity of 2.45 × 10−7, supported by a limit of quantitation of 5 cells per run. Given this high analytical sensitivity, the assay provides a robust negative predictive value, rendering false-negative findings highly unlikely in populations with detectable peripheral disease.

These findings characterize the CellSearch® CMMC assay as a highly sensitive, analytically validated platform for non-invasive deep-MRD level longitudinal surveillance monitoring. When integrated into a clinical workflow that accounts for its specificity profile, the platform offers a patient-friendly complement to serial BM biopsies, with the potential to reduce their frequency in appropriate clinical contexts.

S.P., T.B., D.G., M.L., S.M.J., T.H., F.K., W.S., and Z.S. are employees of Menarini Silicon Biosystems, Inc., the manufacturer of the CellSearch CMMC assay, the CellTracks AutoPrep system, the CellTracks Analyzer II, and the CellRescue Preservative Tubes evaluated in this study. This work was conducted entirely within Menarini Silicon Biosystems, Inc. and received no external funding. The study design, data collection, analysis, and interpretation were performed by employees of the sponsoring organization. The authors declare no other competing interests.

This work was conducted entirely within Menarini Silicon Biosystems, Inc. and received no external funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was conducted in accordance with the Declaration of Helsinki and all applicable federal regulations governing research involving human subjects. Patient peripheral blood samples were procured through two independent commercial biobanks operating under their own institutional ethical oversight: Analytical Biological Services, Inc. (ABS; Exton, PA, USA), under IRB-approved biobank protocols 313965, 311817, and 313063; and Precision Biospecimens (Louisville, KY, USA), under project protocol 064-ONC-26. Informed consent for the collection, storage, and research use of samples was obtained from all donors by the respective biobanks prior to sample provision. Healthy adult donor recruitment was conducted by Menarini Silicon Biosystems, Inc. under institutional protocol VRXHV-02, approved by Advarra Inc. Informed consent was obtained from all healthy donors prior to participation. All samples were de-identified prior to receipt and analysis at Menarini Silicon Biosystems, Inc., and no patient-identifying information was used in any analysis reported herein. All data presented are either aggregated or de-identified in accordance with applicable privacy regulations.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon request to the authors